Sequencing the blood brain barrier in AD

Research Associate | Webber Lab

2023-09-18

Plan

  • background info in vascular stuff (small vessel disease)
  • study design
  • results
  • plan for BHF project

Glossery

  • Infarction: tissue death due to inadequate blood supply
    • Result of prolonged ischaemia, typically due to an artery blockage, rupture or vasoconstriction
    • Resulting lesion is refereed to as an infarct
  • Ischaemia: insufficient supply of oxygen/nutrition to tissue due to disrupted blood supply

Vascular dementia

  • Second most common dementia (~15-30%), and most common secondary dementia
  • Post-stroke 15-30% subjects develop dementia (Pendlebury and Rothwell 2009)
    • Some argue should be viewed as a subtype due to differing pathophysiology

Image depicting 4 MRI brain scans with various vascular damage

Structure of the neurovasculature

An image depicting the cellular structure of the blood vessels in the brain.

Vascular segmentation

An image depicting the cellular segmentation of a blood vessel in the brain

Study design

  • 20 cases + 20 controls post-mortem human brain tissue
  • Parenchyma and vascular fractions (80 samples total) > single cell seq
  • Genotyping pending

A cartoon deliniating the parenchyma and vascular components of the brain

Adapted from Warren (2018)

Data procesing

  • Using scflow

PCA/UMAP

Inverted example slide

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## make a plot
ggplot(diamonds, aes(carat, price, colour = cut)) +
    geom_point() +
    theme_bw() +
    scale_color_viridis_d()

Examples with R code: Tables

## print table
diamonds %>%
  slice_sample(n = 10) %>%
  gt() %>%
  tab_header(title = md("**Table title**"), subtitle = md("A *subtitle*")) %>%
  tab_source_note("Here is some source information")
Table title
A subtitle
carat cut color clarity depth table price x y z
1.02 Ideal D SI1 62.3 56 5266 6.49 6.45 4.03
0.34 Ideal E VS1 60.8 57 1033 4.53 4.49 2.74
0.31 Ideal G SI2 60.5 57 523 4.40 4.36 2.65
1.50 Very Good G SI2 63.1 57 9282 7.29 7.25 4.59
1.23 Ideal H VS2 62.8 56 7900 6.76 6.84 4.27
1.55 Ideal J SI1 61.7 54 7987 7.47 7.50 4.62
1.01 Very Good D SI2 62.9 59 4064 6.29 6.37 3.98
0.30 Ideal F VS1 61.8 55 612 4.31 4.33 2.67
0.61 Premium F VVS1 61.8 59 2753 5.48 5.40 3.36
0.30 Ideal H VS1 61.6 57 526 4.30 4.33 2.66
Here is some source information

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leaflet() %>% 
  addTiles() %>% 
  setView(-0.1371784166832623, 51.52405283300594, zoom = 17)

Examples with R code: HTML Widgets 2

DT::datatable(head(iris, 10), fillContainer = FALSE,
              options = list(pageLength = 6))

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$$\bar{X}=\frac{1}{n}\sum_{i=1}^nX_i$$

\[\bar{X}=\frac{1}{n}\sum_{i=1}^nX_i\]

Diagrams with Mermaid!

Read about how to create a diagram in this post by Mine Çetinkaya-Rundel.

flowchart LR
  A[qmd] --> B(Knitr)
  A[qmd] --> C(Jupyter)
  B(Knitr) --> D[md]
  C(Jupyter) --> D[md]
  D[md] --> E(pandoc)
  E(pandoc) --> F(HTML)
  E(pandoc) --> G(PDF)
  E(pandoc) --> H(Word)
  E(pandoc) --> I{and more}
Figure 1: How Quarto orchestrates rendering of documents: start with a qmd file, use the Knitr or Jupyter engine to perform the computations and convert it to an md file, then use Pandoc to convert to various file formats including HTML, PDF, and Word.

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pagedown::chrome_print("path-to-file.html")

Thanks for listening

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References

Pendlebury, Sarah T., and Peter M. Rothwell. 2009. “Prevalence, Incidence, and Factors Associated with Pre-Stroke and Post-Stroke Dementia: A Systematic Review and Meta-Analysis.” The Lancet Neurology 8 (11): 1006–18. https://doi.org/10.1016/S1474-4422(09)70236-4.
Schaeffer, Samantha, and Costantino Iadecola. 2021. “Revisiting the Neurovascular Unit.” Nature Neuroscience 24 (9): 1198–1209. https://doi.org/10.1038/s41593-021-00904-7.
Warren, Katherine Elizabeth. 2018. “Beyond the Blood:Brain Barrier: The Importance of Central Nervous System (CNS) Pharmacokinetics for the Treatment of CNS Tumors, Including Diffuse Intrinsic Pontine Glioma.” Frontiers in Oncology 8.